PROJECT SUMMARY/ABSTRACT The Cancer Therapeutics Program (CTP) is organized around three Research Themes: 1) Target Identification and Drug Discovery; 2) Drug Development; and 3) Clinical Investigations and Translational Studies. In Theme 1, biomarker and drug leads are discovered by multi-disciplinary teams and subsequently prioritized for further development by Program Leaders. Since many tools used for the development of cancer therapeutics can also be applied for tumor marker, Theme 1 encompasses projects that focus on the following technologies: ?Omics, [genomics, proteomics, metabolomics, and glycomics], combinatorial chemistry, medicinal chemistry, organic synthesis, carbohydrate chemistry and biosynthesis, computational and structural biology [including cryto-TEM, AFM and X-ray crystallography], high-throughput screening, nanotechnology, cancer stem cells, immunotherapy, and microRNA targeting. Theme 2 specifically focuses on preclinical anti- cancer drug development projects, including efforts to understand drug-target interactions, compensatory feedback effects and resistance mechanisms in order to form the basis and rationale for early phase clinical trial investigations. Theme 2 also encompasses the development of robust laboratory resources essential for preclinical drug modeling (e.g., patient derived xenograft [PDX] models and pharmacokinetics). Theme 3 focuses on the direct translation of preclinical models to human applications in the context of clinical trial design and conduct. In addition, Theme 3 also includes biospecimen collection and subsequent bedside-to- bench translational studies of these specimens in order to further evaluate pharmacodynamic effects and resistance mechanisms. The mission of the CTP is realized by the following Specific Aims: 1) Enhance and facilitate intra- programmatic and inter-programmatic interaction and collaboration between basic scientists and clinical investigators in cancer therapeutics; 2) Promote the discovery, development, and application of novel therapeutic approaches; and, 3) Develop translational and laboratory-based clinical investigations of new therapeutic agents and new therapeutic approaches. PROGRAM ASPECTS Co-leaders: Kit S. Lam, MD, PhD; Primo N. Lara, Jr. MD Members: 55 Total Grant Funding (ADC): $8.7 million Total Peer-Reviewed Funding (ADC): $5.2 million Total NCI funding (ADC): $2.2 million Total No. Publications: 824 Inter-programmatic publications: 265 (32.2%) Intra-programmatic publications: 271 (32.9%) Multi-institutional publications: 384 (46.6%) The CTP has 55 members from 14 diverse academic units of UC Davis including Biochemistry and Molecular Medicine, Chemistry, Entomology and Nematology, Biomedical Engineering, Dermatology, Internal Medicine, Molecular and Cellular Biology, Neurology, Obstetrics and Gynecology, Pediatrics, Pharmacology, Radiation Oncology, and Surgery, and 6 different schools highlighting the multidisciplinary focus of the program. The total peer-reviewed, cancer-related funding (annual direct cost) has slightly declined to $5.2 million ($2.2 million NCI) from $8.8 million at the last competitive renewal ($3.8 million NCI) due to sequestration and the transition of Urothelial Cancer-related funding from this program to the new Prostate Urothelial Cancer Program (Program 5). Despite the decrease in funding, our funded projects have increased with 55 peer-review funded projects (27 NCI-funded) compared to 52 peer-review funded projects (25 NCI-funded) at the last competitive renewal.